Vita-Salute San Raffaele University
Experimental Neurophysiology Unit

Author Of 2 Presentations

Neuromyelitis Optica and Anti-MOG Disease Oral Presentation

PS15.03 - Optical coherence tomography in aquaporin-4-IgG positive neuromyelitis optica spectrum disorders: a collaborative multi-center study

Abstract

Background

Optic neuritis (ON) is a frequent manifestation in aquaporin-4 antibody (AQP4-IgG) seropositive neuromyelitis optica spectrum disorders (NMOSD). Due to limited samples, existing optical coherence tomography (OCT) studies are inconsistent regarding retinal changes in eyes with a history of ON (NMO-ON) and without a history of ON (NMO-NON), and their functional relevance.

Objectives

The CROCTINO (Collaborative Retrospective Study on retinal OCT in Neuromyelitis Optica) project aims to reveal correlates of retinal pathology and to generate hypotheses for prospective OCT studies in NMOSD. The objective of this study was to analyze retinal changes of AQP4-IgG seropositive NMO-ON and NMO-NON eyes in an international cross-sectional OCT dataset.

Methods

Of 656 subjects, we enrolled 283 AQP4-IgG seropositive NMOSD patients and 72 healthy controls (HC) from 22 international expert centers. OCT data was acquired with Spectralis SD-OCT, Cirrus HD-OCT and Topcon 3D OCT-1. Mean thickness for the combined ganglion cell and inner plexiform layer (GCIP) and inner nuclear layer (INL) were calculated from macular volume scans. Clinical, functional and laboratory testing were performed at discretion of each center.

Results

We compared NMO-ON eyes (N = 260), NMO-NON eyes (N = 241) and HC eyes (N = 136). GCIP was reduced in NMO-ON (57.4 ± 12.2 µm) compared with NMO-NON (75.9 ± 7.7 µm; p < 0.001) and HC (81.4 ± 5.7 µm; p < 0.001). NMO-NON had thinner GCIP (p < 0.001) compared with HC. INL was thicker in NMO-ON (40.3 ± 3.9 µm) compared with NMO-NON (38.6 ± 3.9µm; p < 0.001), but not HC (39.4 ± 2.6 µm). Microcystic macular edema were visible in 6.6 % of NMOSD eyes.

Conclusions

AQP4-IgG seropositive NMOSD is characterized by a functionally relevant loss of retinal neuroaxonal content and a - probably inflammatory - increase of INL after ON. Our study further supports the existence of attack-independent damage in the visual system of patients with AQP4-IgG seropositive NMOSD.

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Neuro-Ophthalmology Oral Presentation

PS15.05 - Retinal neuro-axonal loss reflects disability accrual in progressive multiple sclerosis independently from disease activity

Speakers
Presentation Number
PS15.05
Presentation Topic
Neuro-Ophthalmology
Lecture Time
13:39 - 13:51

Abstract

Background

The visual pathway has emerged as an elective platform to study the interaction between demyelination and neurodegeneration in multiple sclerosis (MS)

Objectives

We specifically assessed neural damage at this level in progressive MS (PMS), also exploring the evolution over time of functional (trough visual evoked potentials - VEPs) and structural (trough optical coherence tomography - OCT) parameters, as well as their relations with disease course and clinical disability.

Methods

We performed a prospective longitudinal study enrolling 350 PMS patients (228 secondary progressive MS - SPMS, 122 primary progressive MS - PPMS) who underwent a cross-sectional evaluation comprehensive of Expanded Disability Statur Scale (EDSS) assessment, high (HCVA)- and low-contrast (LCLA) visual acuity test, full-field (ff-VEPs) as well as multifocal (mf-VEPs) VEPs, and OCT. We performed a follow-up assessment (mean interval 2.0±0.9 years) in 147 patients (52 PPMS and 95 SPMS); a parallel collection of clinical records (including reports MRI scans, performed as per clinical practice) has been also obtained.

Results

Independently from previous optic neuritis (ON), we found visual conduction to be slower among SPMS compared to PPMS patients, particularly for mf-VEPs: mean latency 168.9 ms (95% CI 166.2-171.1) vs 163.8 ms (95% CI 160.7-166.9) respectively, p=0.019. Retinal Nerve Fiber Layer (RNFL) was also found to be thinner among SPMS in comparison to PPMS patients: mean 83.4 μm (95% CI 81.4-85.4) vs 87.0 μm (95% CI 84.4-89.6), p=0.040, with similar results for Ganglion Cell-Inner Plexiform Layer (GCIPL). Considering the evolution over time of functional and structural parameters, we found no significant differences comparing PPMS and SPMS patients. Reclassifying our cohort according to EDSS status (“stable” vs “worsened”) we found a significant between-groups difference in terms of RNFL evolution: mean annualized percent change -0.163 %/year (95% CI -0.467 - -0.141) vs -0.854 %/year (95% CI -1.188 - -0.521) respectively, p=0.003. Similar findings were obtained for GCIPL change. In both cases, these observations were independent from the evidence of MRI activity during follow-up.

Conclusions

our results suggest the presence of a greater functional and structural involvement of the visual system among SPMS compared to PPMS patients, independently from previous ON history; follow-up data suggest however neurodegeneration accrual over time to be similar between these two clinical subgroups. The longitudinal relation between RNFL - GCIPL thinning and EDSS worsening, even in the absence of overt MRI activity and/or clinical relapses, suggests OCT to represent a useful tool to monitor disease progression and to assess neuroprotection in PMS.

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Author Of 4 Presentations

Clinical Outcome Measures Poster Presentation

P0095 - Intracortical motor conduction is associated with dexterity in progressive multiple sclerosis (ID 1841)

Speakers
Presentation Number
P0095
Presentation Topic
Clinical Outcome Measures

Abstract

Background

Hand dexterity dysfunction is a key feature of disability in people with progressive multiple sclerosis (PMS). It underlies corticospinal tract (CST) and cerebellar integrity but also disruption of cortical networks, which are hardly assessed by standard techniques. Transcranial magnetic stimulation is a promising tool for evaluating the integrity of intracortical motor pathways.

Objectives

to investigate neurophysiological correlates of motor hand impairment in PMS and assess intracortical motor conduction through the use of a innovative TMS protocol.

Methods

Antero-posterior (AP) stimulation of the primary motor cortex activates the CST indirectly through polysynaptic pathways, while a direct CST activation occurs with latero-medial (LM) directed current. 30 PMS and 15 healthy controls underwent dominant hand motor evoked potentials (MEP) using AP and LM-directed stimulation, and a clinical assessment of dexterity (nine-hole peg test) and strength (MRC scale, grip and pinch).

Results

PMS with AP-LM latency difference 2.5 standard deviation above the mean of controls (33%) showed worse dexterity but no difference in upper limb strength. Accordingly, AP-LM latency shortening predicted dexterity (R2 0.538, p<0.001), but not strength impairment. On the contrary, absolute MEP latencies only correlated with strength (grip: R2 0.381, p=0.014; MRC: R2 0.184, p=0.041).

Conclusions

AP-LM latency shortening may be used to assess the integrity polysynaptic intracortical networks implicated in dexterity impairment.

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Neuro-Ophthalmology Poster Presentation

P0767 - Increase Sensitivity in Detecting Neurodegeneration in Multiple Sclerosis: a Voxel-Based Morphometry Study with Optical Coherence Tomography  (ID 1879)

Speakers
Presentation Number
P0767
Presentation Topic
Neuro-Ophthalmology

Abstract

Background

Neurodegeneration of multiple sclerosis (MS) can be measured with optic coherence tomography (OCT), as thinning of peripapillary retinal nerve fiber layer (pRNFL), or as reduced total macula volume (TMV). The macula scan can be further segmented into the ganglion cell layer (GCL), inner plexiform layer (IPL), and inner nuclear layer (INL), which are plausible markers for neuronal loss, dendritic loss, or ongoing inflammation. Unlike traditional method yields only several averaged values of the whole image, voxel-based morphometry (VBM) can visualize and compare the whole macula map, therefore it can be more sensitive in detecting focal lesions.

Objectives

Here we applied VBM to macula OCT in different types of MS and compare the results with traditional parameters such as pRNFL or TMV.

Methods

Three groups of patients with CIS (N=12, 2 male, age=32±12 years, disease duration = 0.9±1.3 years), RRMS (N=9, 6 male, age=32±8 years, disease duration = 1.2±1.2 years), PPMS (N=14, 11 male, age=44±9 years, disease duration = 2.5±1.3 years) and eighteen healthy subjects (4M, age = 29±5 y) were enrolled. Eyes with histories of optic neuritis were excluded. Peripapillary and Macula volume scans were performed and segmented with Heidelberg Spectralis OCT. The segmented thickness maps of RNFL, GCL, IPL, and INL were registered to generate group maps with VBM. total macula volume(TMV) and peripapillary thickness (pRNFL) were compared with healthy with independent t-test, while voxel-wise t-tests were performed between patients and healthy maps with correction of false discovery rate(FDR).

Results

No group difference was found in pRNFL, while the PPMS group showed significantly lower TMV of RNFL, GCL, and IPL. On the other hand, the voxel-wise comparison showed significant differences in all patients’ groups compared with healthy, while the lesion loads in RNFL and GCL showed a gradient increases from CIS to RRMS to PPMS. In the MS groups, the significant atrophy of IPL and thickening in INL co-localized at parafovea, while in CIS group the IPL atrophy located in nasal macula while the INL thickening still located at parafovea.

Conclusions

Our results suggest that applying VBM in macula OCT can increase the detection sensitivity of neurodegeneration in MS patients than traditional measures such as pRNFL or TMV. Also, Common neurodegenerative patterns were found in RNFL and GCL and the lesion load increases with disability, while the difference of IPL and INL differs between MS and CIS cohort and can be a potential biomarker for predicting converters.

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Neuro-Ophthalmology Poster Presentation

P0770 - Serum neurofilaments predict recovery after acute optic neuritis (ID 1885)

Speakers
Presentation Number
P0770
Presentation Topic
Neuro-Ophthalmology

Abstract

Background

Optic neuritis is an immune-mediated disease of the optic nerve, strongly associated with multiple sclerosis (MS). Although the visual prognosis of optic neuritis is generally favourable, the degree of remission varies considerably. The degree of clinical remission is associated with the degree of optic nerve axonal loss, that can be quantified accurately by Optic Coeherence Tomography (OCT). Neurofilament light chain (NfL) is part of the axonal cytoskeletal neurofilaments and is released upon immune-mediated axonal damage during optic neuritis and MS.

Objectives

We aimed to investigate if NfL levels sampled close after symptom onset would predict the outcome after optic neuritis.

Methods

We included 31 patients with optic neuritis as a first demyelinating episode. Patients underwent visual tests, OCT, magnetic resonance imaging (MRI) and lumbar puncture. NfL levels were measured through use of a Simoa HD-1 instrument (Quanterix). Longitudinal changes in inter-ocular difference in visual acuity and OCT parameters were chosen as primary outcome measures of visual loss to account for their inter-individual variability. Multilevel mixed effect models have been used to assess the prognostic factor of baseline NfL levels on longitudinal changes in visual outcomes.

Results

Results: patients (mean age 37.3 years, SD 8.7, 71% females) had a mean follow-up of 27.6 months (SD 12.3). The mean inter-ocular visual acuity difference decreased with the follow-up (baseline 2.8 SD 1.2, follow up 2.1 SD 1.5, p <0.05), while mean inter-ocular RNFL thickness difference significantly increased with time (3.2 SD 10.2 at baseline, 12.7 SD 15.2 at follow-up). Basel NfL levels above 75°ile were significantly associated with an increase in inter-ocular visual acuity difference (B 0.05 SE 0.02, p <0.01) and inter-ocular RNFL thickness difference (B 0.64 SE 0.20, p <0.01).

Conclusions

Conclusion: NfL is a promising biomarker of visual outcome after optic neuritis. This could aid neuroprotective/regenerative medical advancements.

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Rehabilitation and Comprehensive Care Poster Presentation

P1096 - Evaluating Effects of Global Proprioceptive Resonance on Gait in Multiple Sclerosis with Kinetic and Electromyography  (ID 1871)

Speakers
Presentation Number
P1096
Presentation Topic
Rehabilitation and Comprehensive Care

Abstract

Background

Global proprioceptive resonance (GPR) mechanically induces multifocal vibration at specific frequency among various cutaneous mechanoreceptors. Preliminary results suggest that GPR can modulate neuromuscular and neuroendocrine systems, therefore it may improve muscle strength and facilitate Lactose metabolism. Therefore, GPR could be beneficial for patients with multiple sclerosis (PwMS) since muscle weakness is an important factor of their gait impairment.

Objectives

Here we evaluated the acute effects of a single GPR session on gait pattern in patients with MS using wearable sensors to quantitatively measure surface electromyography (sEMG) and body acceleration during walking.

Methods

Ten patients with MS(PwMS, 8 males; mean age: 48±9.1 years; mean EDSS: 5.9±0.74), in a randomized order, underwent 15 minutes GPR and sham session(Keope GPR, ANDROMEDA, Italy) with a week interval. Nine Hole Peg Test(9HPT) and 6-meter-walking-test(SMWT) were performed pre- and immediately after the sessions. During SMWT, surface EMG and body acceleration were recorded with a wearable accelerator and surface electrodes(BTS Bioengineering, Italy). The SMWT were performed with spontaneous(Vp) and maximum velocity(Vmax). Time of 9HPT, velocity, cadence, step length and Coactivation index(CoI) of MWT of pre- and post-GPR were calculated for further statistics.

Results

Compared with sham stimulus, significant improvement was found in 9HPT(p=.02) of the dominant hand after the active GPR session. For SMWT, increased velocity(p = .05) and cadence(p =.03) after active stimulus was found under Vp condition only, but not in the Vmax condition. No significant difference was found in other parameters.

Conclusions

Our preliminary results suggest that a single active GPR session can improve the motor performance in both upper and lower limbs. Our results suggest that GPR could boost muscle recovery and can be beneficial to be incorporated into rehabilitation protocols to ameliorate the fatigue level for PwMS.

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Presenter Of 2 Presentations

Clinical Outcome Measures Poster Presentation

P0031 - Asymptomatic anterior optic pathway involvement in early multiple sclerosis and clinically isolated syndromes (ID 1838)

Speakers
Presentation Number
P0031
Presentation Topic
Clinical Outcome Measures

Abstract

Background

Optical coherence tomography is gaining increasing relevance in the assessment of people with multiple sclerosis. Converging evidence point to the view that neuro-retinal changes, in eyes without acute optic neuritis, reflect inflammatory and neurodegenerative processes taking place throughout the CNS.

Objectives

The present study aims at exploring the usefulness of optical coherence tomography as a marker of inflammation and disease burden in the earliest phases of the disease.

Methods

a cohort of 150 consecutive patients underwent clinical, neurophysiological and brain MRI assessment as well as lumbar puncture as part of their diagnostic workup for a neurological episode suggestive of inflammatory CNS disorder. For the present study, patients also received a visual pathway assessment - including OCT, VEP, visual acuity testing –, measurement of CSF inflammatory markers – a set of 17 cytokines-chemokines and, count of extracellular vesicles of myeloid origin –, and dosage of serum neurofilaments.

Results

19.2% of clinically isolated syndromes had abnormal visual evoked potentials in eyes without optic neuritis. Similarly, optical coherence tomography identified neuro-retinal thinning in 17.8% of patients without prior visual symptoms. The presence of asymptomatic involvement of the anterior optic pathway tested with either techniques was associated with a greater disease burden.

A thinner ganglion cell layer in eyes without prior optic neuritis or instrumental evidences of it was correlated with higher EDSS, lower low contrast visual acuity, longer disease duration, higher brain lesion load, presence of gadolinium enhancing lesions, more severe abnormalities along motor and somatosensory evoked potentials, and higher frequency of CSF-specific oligoclonal bands.

We also found that inner nuclear layer thickens in a post-acute (1.1 – 3.7 months) phase after a relapse, particularly in those who did not receive steroid treatment. Likewise, a longitudinal analysis on 65 patients, showed that this swelling is transient and returns to normal values after one year of follow-up. Notwithstanding, the clinical, MRI, serological and CSF markers of disease activity considered in the study were strictly associated with one-another but none of them was associated with inner nuclear layer volume.

Conclusions

The present findings suggest that instrumental evidence of asymptomatic optic nerve involvement is associated with a greater disease burden in early MS and clinically isolated syndrome. Neuro-retinal changes are present since the earliest phases of the disease and yield important information regarding the neurodegenerative and inflammatory processes occurring in the CNS.

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Clinical Outcome Measures Poster Presentation

P0095 - Intracortical motor conduction is associated with dexterity in progressive multiple sclerosis (ID 1841)

Speakers
Presentation Number
P0095
Presentation Topic
Clinical Outcome Measures

Abstract

Background

Hand dexterity dysfunction is a key feature of disability in people with progressive multiple sclerosis (PMS). It underlies corticospinal tract (CST) and cerebellar integrity but also disruption of cortical networks, which are hardly assessed by standard techniques. Transcranial magnetic stimulation is a promising tool for evaluating the integrity of intracortical motor pathways.

Objectives

to investigate neurophysiological correlates of motor hand impairment in PMS and assess intracortical motor conduction through the use of a innovative TMS protocol.

Methods

Antero-posterior (AP) stimulation of the primary motor cortex activates the CST indirectly through polysynaptic pathways, while a direct CST activation occurs with latero-medial (LM) directed current. 30 PMS and 15 healthy controls underwent dominant hand motor evoked potentials (MEP) using AP and LM-directed stimulation, and a clinical assessment of dexterity (nine-hole peg test) and strength (MRC scale, grip and pinch).

Results

PMS with AP-LM latency difference 2.5 standard deviation above the mean of controls (33%) showed worse dexterity but no difference in upper limb strength. Accordingly, AP-LM latency shortening predicted dexterity (R2 0.538, p<0.001), but not strength impairment. On the contrary, absolute MEP latencies only correlated with strength (grip: R2 0.381, p=0.014; MRC: R2 0.184, p=0.041).

Conclusions

AP-LM latency shortening may be used to assess the integrity polysynaptic intracortical networks implicated in dexterity impairment.

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